arXiv subjects

Yuancheng Sun

Publications and source records attributed to Yuancheng Sun.

5 recordsLinked to original sources

arXiv2025

EPO: Diverse and Realistic Protein Ensemble Generation via Energy Preference Optimization

Accurate exploration of protein conformational ensembles is essential for uncovering function but remains hard because molecular-dynamics (MD) simulations suffer from high computational costs and energy-barrier trapping. This paper presents Energy Preference Optimization (EPO), an online refinement algorithm that turns a pretrained protein ensemble generator into an energy-aware sampler without extra MD trajectories. Specifically, EPO leverages stochastic differential equation sampling to explore the conformational landscape and incorporates a novel energy-ranking mechanism based on list-wise preference optimization. Crucially, EPO introduces a practical upper bound to efficiently approximate the intractable probability of long sampling trajectories in continuous-time generative models, making it easily adaptable to existing pretrained generators. On Tetrapeptides, ATLAS, and Fast-Folding benchmarks, EPO successfully generates diverse and physically realistic ensembles, establishing a new state-of-the-art in nine evaluation metrics. These results demonstrate that energy-only preference signals can efficiently steer generative models toward thermodynamically consistent conformational ensembles, providing an alternative to long MD simulations and widening the applicability of learned potentials in structural biology and drug discovery.

cs.LG↗

arXiv2025

STELLA: A Multimodal LLM for Protein Functional Annotation via Unified Sequence-Structure Encoding

Understanding the intricate interplay among sequence, structure, and function remains a fundamental challenge in proteomics. The sequence-structure-function paradigm posits that biological roles are governed by the tertiary geometric conformations encoded within primary sequences; consequently, integrating these multi-modal descriptors is imperative for accurate functional annotation. While protein language models (pLMs) have achieved significant progress via representation learning on massive sequence data, they often lack the capacity to incorporate high-resolution structural information and the rich textual context that characterizes protein roles. In this work, we present STELLA, a multimodal LLM that synergistically aligns bimodal (sequence-structure) representations with the textual modality to advance protein functional annotation. By leveraging ESM3 for unified bimodal encoding and Llama-3.1-8B-Instruct for natural language modeling, STELLA achieves state-of-the-art performance in two critical tasks: Functional Description Prediction and Enzyme-catalyzed Reaction Prediction. This study demonstrates that multimodal LLMs represent a paradigm shift beyond pure pLMs, offering a new frontier for protein biology and biomedical discovery. The codes can be accessed via https://github.com/ocx-lab/STELLA.

q-bio.BM↗

arXiv2024

Constraint Decoupled Latent Diffusion for Protein Backmapping

Coarse-grained (CG) molecular dynamics simulations enable efficient exploration of protein conformational ensembles. However, reconstructing atomic details from CG structures (backmapping) remains a challenging problem. Current approaches face an inherent trade-off between maintaining atomistic accuracy and exploring diverse conformations, often necessitating complex constraint handling or extensive refinement steps. To address these challenges, we introduce a novel two-stage framework, named CODLAD (COnstraint Decoupled LAtent Diffusion). This framework first compresses atomic structures into discrete latent representations, explicitly embedding structural constraints, thereby decoupling constraint handling from generation. Subsequently, it performs efficient denoising diffusion in this latent space to produce structurally valid and diverse all-atom conformations. Comprehensive evaluations on diverse protein datasets demonstrate that CODLAD achieves state-of-the-art performance in atomistic accuracy, conformational diversity, and computational efficiency while exhibiting strong generalization across different protein systems. Code is available at https://github.com/xiaoxiaokuye/CODLAD.

cs.LG↗

arXiv2024

Pre-training with Fractional Denoising to Enhance Molecular Property Prediction

Deep learning methods have been considered promising for accelerating molecular screening in drug discovery and material design. Due to the limited availability of labelled data, various self-supervised molecular pre-training methods have been presented. While many existing methods utilize common pre-training tasks in computer vision (CV) and natural language processing (NLP), they often overlook the fundamental physical principles governing molecules. In contrast, applying denoising in pre-training can be interpreted as an equivalent force learning, but the limited noise distribution introduces bias into the molecular distribution. To address this issue, we introduce a molecular pre-training framework called fractional denoising (Frad), which decouples noise design from the constraints imposed by force learning equivalence. In this way, the noise becomes customizable, allowing for incorporating chemical priors to significantly improve molecular distribution modeling. Experiments demonstrate that our framework consistently outperforms existing methods, establishing state-of-the-art results across force prediction, quantum chemical properties, and binding affinity tasks. The refined noise design enhances force accuracy and sampling coverage, which contribute to the creation of physically consistent molecular representations, ultimately leading to superior predictive performance.

cs.LG↗

arXiv2022

PEMP: Leveraging Physics Properties to Enhance Molecular Property Prediction

Molecular property prediction is essential for drug discovery. In recent years, deep learning methods have been introduced to this area and achieved state-of-the-art performances. However, most of existing methods ignore the intrinsic relations between molecular properties which can be utilized to improve the performances of corresponding prediction tasks. In this paper, we propose a new approach, namely Physics properties Enhanced Molecular Property prediction (PEMP), to utilize relations between molecular properties revealed by previous physics theory and physical chemistry studies. Specifically, we enhance the training of the chemical and physiological property predictors with related physics property prediction tasks. We design two different methods for PEMP, respectively based on multi-task learning and transfer learning. Both methods include a model-agnostic molecule representation module and a property prediction module. In our implementation, we adopt both the state-of-the-art molecule embedding models under the supervised learning paradigm and the pretraining paradigm as the molecule representation module of PEMP, respectively. Experimental results on public benchmark MoleculeNet show that the proposed methods have the ability to outperform corresponding state-of-the-art models.

q-bio.BM↗